The investigators seek support for an exploratory/developmental research project that will offer new insights into the complex biology and pathophysiology underlying the geriatric syndrome of frailty. Frailty is a topic of great clinical importance to geriatric medicine, but research has been hampered by a lack of an agreed-upon definition of frailty. Valid operational definitions of frailty could greatly enhance research on the causes and consequences of frailty. Though numerous definitions of "frailty" have been proposed in the published literature, the term has usually been used clinically as a global concept to describe a condition, common in the very old, of impaired strength and endurance, increased vulnerability to stressors, and increased risk for morbidity, disability and mortality. In a landmark paper in 2001, Fried and colleagues used data from the Cardiovascular Health Study (CHS) and defined a phenotype of frailty to include 3 or more of the following: unintentional weight loss, weakness, exhaustion, slow gait, and low physical activity level. Older adults found to be frail using this definition were at increased risk for adverse health outcomes, independent of their sociodemographic characteristics, medical comorbidities, and level of disability. This definition provides a useful operational starting point in the quest towards understanding and ultimately preventing and treating frailty, but empiric support of its construct validity is incomplete. This multidisciplinary team proposes to use data previously-collected in the MacArthur Study of Successful Aging (MSSA), a longitudinal cohort study of 1189 older adults, to: 1) use structural equation modeling to test the construct validity of the selected CHS criteria; 2) empirically explore whether the CHS definition of frailty could be enhanced by expanding the definition to include differing criteria that have been hypothesized to be part of frailty (such as cognitive impairment); 3) test whether geriatric frailty is represented by correlated sub-phenotypes (physical, cognitive, behavioral and inflammatory) with different characteristic patterns; and 5) examine the potential role of neuroendocrine, psychosocial and sociodemographic characteristics in predicting frailty. The MSSA offers an extraordinary opportunity to gain new insights into the geriatric syndrome of frailty because this rich dataset includes measures of all 5 of the criteria used in CHS to define frailty, and it also includes rigorous measures of disability and comorbidity, serum markers of inflammation, urine markers of neuroendocrine dysregulation, detailed measures of cognitive function, long-term hospitalization and mortality data, as well as measures of many psychosocial constructs that may be associated with frailty. In summary, this exploratory investigation offers a unique and cost-effective means to break new ground in our understanding of the geriatric syndrome of frailty. [unreadable] [unreadable] [unreadable]